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Biophys J, March 2001, p. 1251-1261, Vol. 80, No. 3

Synapse-Specific Contribution of the Variation of Transmitter Concentration to the Decay of Inhibitory Postsynaptic Currents

Zoltan Nusser,* David Naylor,dagger and Istvan Mody*

 *Department of Neurology, UCLA School of Medicine, and  dagger VA Greater Los Angeles Health Care System, Los Angeles, California 90095-1769 USA

Synaptic transmission is characterized by a remarkable trial-to-trial variability in the postsynaptic response, influencing the way in which information is processed in neuronal networks. This variability may originate from the probabilistic nature of quantal transmitter release, from the stochastic behavior of the receptors, or from the fluctuation of the transmitter concentration in the cleft. We combined nonstationary noise analysis and modeling techniques to estimate the contribution of transmitter fluctuation to miniature inhibitory postsynaptic current (mIPSC) variability. A substantial variability (~30%) in mIPSC decay was found in all cell types studied (neocortical layer2/3 pyramidal cells, granule cells of the olfactory bulb, and interneurons of the cerebellar molecular layer). This large variability was not solely the consequence of the expression of multiple types of GABAA receptors, as a similar mIPSC decay variability was observed in cerebellar interneurons that express only a single type (alpha 1beta 2gamma 2) of GABAA receptor. At large synapses on these cells, all variance in mIPSC decay could be accounted for by the stochastic behavior of ~36 pS channels, consistent with the conductance of alpha 1beta 2gamma 2 GABAA receptors at physiological temperatures. In contrast, at small synapses, a significant amount of variability in the synaptic cleft GABA transient had to be present to account for the additional variance in IPSC decay over that produced by stochastic channel openings. Thus, our results suggest a synapse-specific contribution of the variation of the spatiotemporal profile of GABA to the decay of IPSCs.

Biophys J, March 2001, p. 1251-1261, Vol. 80, No. 3
© 2001 by the Biophysical Society   0006-3495/01/03/1251/11  $2.00


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